Institute of Fundamental Technological Research
Polish Academy of Sciences

Staff

Alicja Kosik-Kozioł, PhD

Department of Biosystems and Soft Matter (ZBiMM)
Division of Modelling in Biology and Medicine (PMBM)
position: Assistant Professor
telephone: (+48) 22 826 12 81 ext.: 330
room: 320
e-mail:
ORCID: 0000-0002-2607-7271

Doctoral thesis
2020-09-15 Three-dimensional tissue scaffolds fabrication for Osteochondral Tissue Engineering  (Politechnika Warszawska)
supervisor -- Wojciech Święszkowski, PhD, DSc, PW
 

Recent publications
1.  Ziai Y., Lanzi M., Rinoldi C., Zargarian Seyed S., Zakrzewska A., Kosik-Kozioł A., Nakielski P., Pierini F., Developing strategies to optimize the anchorage between electrospun nanofibers and hydrogels for multi-layered plasmonic biomaterials, Nanoscale Advances, ISSN: 2516-0230, DOI: 10.1039/d3na01022h, pp.1-13, 2024

Abstract:
Polycaprolactone (PCL), a recognized biopolymer, has emerged as a prominent choice for diverse biomedical endeavors due to its good mechanical properties, exceptional biocompatibility, and tunable properties. These attributes render PCL a suitable alternative biomaterial to use in biofabrication, especially the electrospinning technique, facilitating the production of nanofibers with varied dimensions and functionalities. However, the inherent hydrophobicity of PCL nanofibers can pose limitations. Conversely, acrylamide-based hydrogels, characterized by their interconnected porosity, significant water retention, and responsive behavior, present an ideal matrix for numerous biomedical applications. By merging these two materials, one can harness their collective strengths while potentially mitigating individual limitations. A robust interface and effective anchorage during the composite fabrication are pivotal for the optimal performance of the nanoplatforms. Nanoplatforms are subject to varying degrees of tension and physical alterations depending on their specific applications. This is particularly pertinent in the case of layered nanostructures, which require careful consideration to maintain structural stability and functional integrity in their intended applications. In this study, we delve into the influence of the fiber dimensions, orientation and surface modifications of the nanofibrous layer and the hydrogel layer's crosslinking density on their intralayer interface to determine the optimal approach. Comprehensive mechanical pull-out tests offer insights into the interfacial adhesion and anchorage between the layers. Notably, plasma treatment of the hydrophobic nanofibers and the stiffness of the hydrogel layer significantly enhance the mechanical effort required for fiber extraction from the hydrogels, indicating improved anchorage. Furthermore, biocompatibility assessments confirm the potential biomedical applications of the proposed nanoplatforms.

Affiliations:
Ziai Y. - IPPT PAN
Lanzi M. - University of Bologna (IT)
Rinoldi C. - IPPT PAN
Zargarian Seyed S. - IPPT PAN
Zakrzewska A. - IPPT PAN
Kosik-Kozioł A. - IPPT PAN
Nakielski P. - IPPT PAN
Pierini F. - IPPT PAN
2.  Nakielski P., Rybak D., Jezierska-Woźniak K., Rinoldi C., Sinderewicz E., Staszkiewicz-Chodor J., Haghighat Bayan Mohammad A., Czelejewska W., Urbanek-Świderska O., Kosik-Kozioł A., Barczewska M., Skomorowski M., Holak P., Lipiński S., Maksymowicz W., Pierini F., Minimally invasive intradiscal delivery of BM-MSCs via fibrous microscaffold carriers, ACS Applied Materials and Interfaces, ISSN: 1944-8244, DOI: 10.1021/acsami.3c11710, pp.1-16, 2023

Abstract:
Current treatments of degenerated intervertebral discs often provide only temporary relief or address specific causes, necessitating the exploration of alternative therapies. Cell-based regenerative approaches showed promise in many clinical trials, but
limitations such as cell death during injection and a harsh disk environment hinder their effectiveness. Injectable microscaffolds offer a solution by providing a supportive microenvironment for cell delivery and enhancing bioactivity. This study evaluated the
safety and feasibility of electrospun nanofibrous microscaffolds modified with chitosan (CH) and chondroitin sulfate (CS) for treating degenerated NP tissue in a large animal model. The microscaffolds facilitated cell attachment and acted as an effective delivery system, preventing cell leakage under a high disc pressure. Combining microscaffolds with bone marrow-derived mesenchymal stromal cells demonstrated no cytotoxic effects and proliferation over the entire microscaffolds. The administration of cells attached to microscaffolds into the NP positively influenced the regeneration process of the intervertebral disc. Injectable poly(L-lactide-co-glycolide) and poly(L-lactide) microscaffolds enriched with CH or CS, having a fibrous structure, showed the potential to promote intervertebral disc regeneration. These features collectively address critical challenges in the fields of tissue engineering and regenerative medicine, particularly in the context of intervertebral disc degeneration.

Keywords:
microscaffolds,cell carriers,injectable biomaterials,intervertebral disc,laser micromachining,electrospinning

Affiliations:
Nakielski P. - IPPT PAN
Rybak D. - IPPT PAN
Jezierska-Woźniak K. - other affiliation
Rinoldi C. - IPPT PAN
Sinderewicz E. - other affiliation
Staszkiewicz-Chodor J. - other affiliation
Haghighat Bayan Mohammad A. - IPPT PAN
Czelejewska W. - other affiliation
Urbanek-Świderska O. - IPPT PAN
Kosik-Kozioł A. - IPPT PAN
Barczewska M. - University of Warmia and Mazury in Olsztyn (PL)
Skomorowski M. - other affiliation
Holak P. - other affiliation
Lipiński S. - other affiliation
Maksymowicz W. - University of Warmia and Mazury in Olsztyn (PL)
Pierini F. - IPPT PAN
3.  Kosik-Kozioł A., Heljak M., Święszkowski W., Mechanical properties of hybrid triphasic scaffolds for osteochondral tissue engineering, Materials Letters, ISSN: 0167-577X, DOI: 10.1016/j.matlet.2019.126893, Vol.261, pp.126893-1-5, 2020

Abstract:
Reproducing the advanced complexity of native tissue by means of the 3D multi-functional construct is a promising tissue engineering approach to osteochondral tissue regeneration. In this study, we present a porous 3D construct composed of three zones responsible for the regeneration of non-calcified cartilage, calcified cartilage and subchondral bone. These three zones of the hybrid were composed of modified biopolymers: (i) alginate (Alg) reinforced by short polylactide (PLA) fibres, (ii) alginate and gelatine methacrylate (GelMA) combined with ß-tricalcium phosphate particles (TCP), (iii) 3D printed polycaprolactone scaffold subsequently modified with the use of an innovative solvent treatment method based on acetone and ultrasound stimulation, respectively. Combining the advanced deposition systems based on: (i) 3D printing coupled with a spray crosslinking system, (ii) an innovative deposition system based on a coaxial-needle extruder, (iii) fused deposition modelling (FDM) connected with post-fabrication treatment, allows us to fabricate the triphasic construct that emulates the structure and properties of the native osteochondral tissue. The aim of the study was to investigate the mechanical properties of the fabricated hybrid and its individual zones. Our results demonstrate the load-bearing capabilities of TC, but nevertheless it should be implanted below the surface line of host cartilage to protect it from strong stresses, at the same time allowing native host tissues to grow into it.

Keywords:
Triphasic scaffold, Osteochondral tissue engineering, Mechanical properties, Hydrogel with nanofillers, Modified PCL

Affiliations:
Kosik-Kozioł A. - other affiliation
Heljak M. - Warsaw University of Technology (PL)
Święszkowski W. - other affiliation
4.  Kosik-Kozioł A., Graham E., Jaroszewicz J., Chlanda A., Kumar P.S., IvanovskI S., Święszkowski W., Vaquette C., Surface Modification of 3D Printed Polycaprolactone Constructs via a Solvent Treatment: Impact on Physical and Osteogenic Properties, ACS BIOMATERIALS SCIENCE & ENGINEERING, ISSN: 2373-9878, DOI: 10.1021/acsbiomaterials.8b01018, Vol.5, No.1, pp.318-328, 2019

Abstract:
One promising strategy to reconstruct bone defects relies on 3D printed porous structures. In spite of several studies having been carried out to fabricate controlled, interconnected porous constructs, the control over surface features at, or below, the microscopic scale remains elusive for 3D polymeric scaffolds. In this study, we developed and refined a methodology which can be applied to homogeneously and reproducibly modify the surface of polymeric 3D printed scaffolds. We have demonstrated that the combination of a polymer solvent and the utilization of ultrasound was essential for achieving appropriate surface modification without damaging the structural integrity of the construct. The modification created on the scaffold profoundly affected the macroscopic and microscopic properties of the scaffold with an increased roughness, greater surface area, and reduced hydrophobicity. Furthermore, to assess the performance of such materials in bone tissue engineering, human mesenchymal stem cells (hMSC) were cultured in vitro on the scaffolds for up to 7 days. Our results demonstrate a stronger commitment toward early osteogenic differentiation of hMSC. Finally, we demonstrated that the increased in the specific surface area of the scaffold did not necessarily correlate with improved adsorption of protein and that other factors, such as surface chemistry and hydrophilicity, may also play a major role.

Keywords:
surface modification, solvent treatment, polycaprolactone, BMP-2 adsorption

Affiliations:
Kosik-Kozioł A. - other affiliation
Graham E. - other affiliation
Jaroszewicz J. - other affiliation
Chlanda A. - Warsaw University of Technology (PL)
Kumar P.S. - other affiliation
IvanovskI S. - other affiliation
Święszkowski W. - other affiliation
Vaquette C. - other affiliation
5.  Kosik-Kozioł A., Costantini M., Mróz A., Idaszek J., Heljak M., Jaroszewicz J., Kijeńska E., Szöke K., Frerker N., Barbetta A., Brinchmann J.E., Święszkowski W., 3D bioprinted hydrogel model incorporating β-tricalcium phosphate for calcified cartilage tissue engineering, Biofabrication, ISSN: 1758-5082, DOI: 10.1088/1758-5090/ab15cb, Vol.11, No.3, pp.035016-1-29, 2019

Abstract:
One promising strategy to reconstruct osteochondral defects relies on 3D bioprinted three-zonal structures comprised of hyaline cartilage, calcified cartilage, and subchondral bone. So far, several studies have pursued the regeneration of either hyaline cartilage or bone in vitro while—despite its key role in the osteochondral region—only few of them have targeted the calcified layer. In this work, we present a 3D biomimetic hydrogel scaffold containing β-tricalcium phosphate (TCP) for engineering calcified cartilage through a co-axial needle system implemented in extrusion-based bioprinting process. After a thorough bioink optimization, we showed that 0.5% w/v TCP is the optimal concentration forming stable scaffolds with high shape fidelity and endowed with biological properties relevant for the development of calcified cartilage. In particular, we investigate the effect induced by ceramic nano-particles over the differentiation capacity of bioprinted bone marrow-derived human mesenchymal stem cells in hydrogel scaffolds cultured up to 21 d in chondrogenic media. To confirm the potential of the presented approach to generate a functional in vitro model of calcified cartilage tissue, we evaluated quantitatively gene expression of relevant chondrogenic (COL1, COL2, COL10A1, ACAN) and osteogenic (ALPL, BGLAP) gene markers by means of RT-qPCR and qualitatively by means of fluorescence immunocytochemistry.

Keywords:
alginate, gelatin methacrylate, ß-tricalcium phosphate TCP, bioprinting, coaxial needle, calcified cartilage

Affiliations:
Kosik-Kozioł A. - other affiliation
Costantini M. - Sapienza University of Rome (IT)
Mróz A. - other affiliation
Idaszek J. - other affiliation
Heljak M. - Warsaw University of Technology (PL)
Jaroszewicz J. - other affiliation
Kijeńska E. - other affiliation
Szöke K. - other affiliation
Frerker N. - other affiliation
Barbetta A. - Sapienza University of Rome (IT)
Brinchmann J.E. - other affiliation
Święszkowski W. - other affiliation
6.  Heljak M.K., Moczulska-Heljak M., Choińska E., Chlanda A., Kosik-Kozioł A., Jaroszewicz T., Jaroszewicz J., Święszkowski W., Micro and nanoscale characterization of poly(DL-lactic-co-glycolic acid) films subjected to the L929 cells and the cyclic mechanical load, Micron, ISSN: 0968-4328, DOI: 10.1016/j.micron.2018.09.004, Vol.115, pp.64-72, 2018

Abstract:
In this paper, the effect of the presence of L929 fibroblast cells and a cyclic load application on the kinetics of the degradation of amorphous PLGA films was examined. Complex micro and nano morphological, mechanical and physico-chemical studies were performed to assess the degradation of the tested material. For this purpose, molecular weight, glass transition temperature, specimen morphology (SEM, μCT) and topography (AFM) as well as the stiffness of the material were measured. The study showed that the presence of living cells along with a mechanical load accelerates the PLGA degradation in comparison to the degradation occurring in acellular media: PBS and DMEM. The drop in molecular weight observed was accompanied by a distinct increase in the tensile modulus and surface roughness, especially in the case of the film degradation in the presence of cells. The suspected cause of the rise in stiffness during the degradation of PLGA films is a reduction in the molecular mobility of the distinctive superficial layer resulting from severe structural changes caused by the surface degradation. In conclusion, all the micro and nanoscale properties of amorphous PLGA considered in the study are sensitive to the presence of L929 cells, as well as to a cyclic load applied during the degradation process.

Keywords:
L929, aliphatic polyester, stiffness rise

Affiliations:
Heljak M.K. - Warsaw University of Technology (PL)
Moczulska-Heljak M. - other affiliation
Choińska E. - Warsaw University of Technology (PL)
Chlanda A. - Warsaw University of Technology (PL)
Kosik-Kozioł A. - other affiliation
Jaroszewicz T. - Warsaw University of Technology (PL)
Jaroszewicz J. - other affiliation
Święszkowski W. - other affiliation
7.  Kosik-Kozioł A., Costantini M., Bolek T., Szöke K., Barbetta A., Brinchmann J., Święszkowski W., PLA short sub-micron fiber reinforcement of 3D bioprinted alginate constructs for cartilage regeneration, Biofabrication, ISSN: 1758-5082, DOI: 10.1088/1758-5090/aa90d7, Vol.9, No.4, pp.044105-1-13, 2017

Abstract:
In this study, we present an innovative strategy to reinforce 3D-printed hydrogel constructs for cartilage tissue engineering by formulating composite bioinks containing alginate and short sub-micron polylactide (PLA) fibers. We demonstrate that Young's modulus obtained for pristine alginate constructs (6.9 ± 1.7 kPa) can be increased threefold (up to 25.1 ± 3.8 kPa) with the addition of PLA short fibers. Furthermore, to assess the performance of such materials in cartilage tissue engineering, we loaded the bioinks with human chondrocytes and cultured in vitro the bioprinted constructs for up to 14 days. Live/dead assays at day 0, 3, 7 and 14 of in vitro culture showed that human chondrocytes were retained and highly viable (∼80%) within the 3D deposited hydrogel filaments, thus confirming that the fabricated composites materials represent a valid solution for tissue engineering applications. Finally, we show that the embedded chondrocytes during all the in vitro culture maintain a round morphology, a key parameter for a proper deposition of neocartilage extracellular matrix.

Keywords:
alginate, PLA, short fibers, hydrogel reinforcement, chondrocytes

Affiliations:
Kosik-Kozioł A. - other affiliation
Costantini M. - Sapienza University of Rome (IT)
Bolek T. - other affiliation
Szöke K. - other affiliation
Barbetta A. - Sapienza University of Rome (IT)
Brinchmann J. - other affiliation
Święszkowski W. - other affiliation
8.  Kosik-Kozioł A, Luchowska U., Święszkowski W., Electrolyte alginate/poly-l-lysine membranes for connective tissue development, Materials Letters, ISSN: 0167-577X, DOI: 10.1016/j.matlet.2016.08.032, Vol.184, No.1, pp.104-107, 2016

Abstract:
The aim of this study was to change the surface of sodium alginate hydrogel by electrostatic binding of poly-l-lysine (PLL) in order to provide more advantageous conditions for connective tissue development. Its impact on L929 mouse fibroblast adhesion, morphology and viability was investigated. Analysis of the material microstructure has shown that performed modification increased surface roughness. It also altered the swelling properties of alginate hydrogel, resulting in less rapid water absorption. Mouse fibroblasts seeded on regular alginate and alginate modified with PLL exhibited different behaviour. The presence of PLL turned out to promote cell adhesion and F-actin spreading, resulting in significantly increased number of viable cells 96 h after seeding.

Keywords:
Alginate, Poly-l-lysine, Electrolyte membranes, Cell adhesion

Affiliations:
Kosik-Kozioł A - other affiliation
Luchowska U. - other affiliation
Święszkowski W. - other affiliation
9.  Wszola M., Idaszek J., Berman A., Kosik-Kozioł A, Gorski L., Jozwik A., Dobrzyn A., Cudnoch-Jędrzejewska A., Kaminski A., Wrzesien R., Serwanska-Swietek M., Chmura A., Kwiatkowski A., Święszkowski W., Bionic Pancreas and Bionic Organs – how far we are from the success, Medtube Science, ISSN: 2353-5695, Vol.3, No.3, pp.25-27, 2015

Abstract:
The progress in the treatment of chronic diseases of civilization that occurred in recent years, led to a significant prolongation of median survival time of the developed countries societies. Organ transplantation has revolutionized medicine as it became possible to replace an irreversibly diseased organ. However, at the moment we can observe a significant shortage of organs for transplantation, which forces doctors to accept those coming from more and more expanding criteria donors. No doubt, the number of donors, at best, will certainly not grow. Tissue engineering and regenerative medicine methods are extremely promising, in particular bioprinting of tissues and organs, which begun to develop at the beginning of the XXI century. Article highlights possible future direction of organ transplantation.

Affiliations:
Wszola M. - other affiliation
Idaszek J. - other affiliation
Berman A. - other affiliation
Kosik-Kozioł A - other affiliation
Gorski L. - other affiliation
Jozwik A. - other affiliation
Dobrzyn A. - other affiliation
Cudnoch-Jędrzejewska A. - other affiliation
Kaminski A. - other affiliation
Wrzesien R. - other affiliation
Serwanska-Swietek M. - other affiliation
Chmura A. - other affiliation
Kwiatkowski A. - Military Institute of Medicine (PL)
Święszkowski W. - other affiliation

Conference abstracts
1.  Kosik-Kozioł A., Rybak D., Rinoldi C., Nakielski P., Pierini F., Ferment Oil-Laden Core-Shell Electrospun Nanofibers for Wound Healing Application , Frontiers in Polymer Science 2023 — Seventh International Symposium Frontiers in Polymer Science, 2023-05-30/06-01, Gothenburg (SE), pp.P2.062-P2.062, 2023

Abstract:
Hard-to-heal wounds represent a significant public health problem that often carries a considerable risk of health complications with a negative impact on the quality of a patient's life [1]. The lack of effective treatments for skin damage can be attributed in part to the complexity of a physiological process occurring during the healing and microbial invasion from both resident and exogenous bacteria [2,3]. This research aimed to meet these challenges by developing a multifunctional core-shell nanofiber scaffold releasing the drugs and consisted antimicrobial peptides that hinder bacterial colonization while accelerating the healing process. Core-shell electrospun naofiber systems can control the biomolecule release profile providing sustainable drugs for wound healing. Implemented antimicrobial peptides effectively destroy a large spectrum of pathogens by contact with the cell membrane, decreasing the rate of antibiotic resistance in our healthcare system. The combination of the coaxial system with electrospinning allowed to obtain well-defined fibers. In this study, highly hydrophilic polyvinyl alcohol was confined into water-stable electrospun fibers using optimized polymer blends and cross-linking methods. All employed structures showed ideal morphology, construct's stability over time, and appropriate drug release profile as well as high-cell viability and antimicrobial properties. The developed multifunctional platforms represent a robust and valid candidate for fabricating skin dressings, accelerating the healing of patients' wounds while protecting against bacterial infection.

Keywords:
electrospinning, PVA, Green crosslinking

Affiliations:
Kosik-Kozioł A. - IPPT PAN
Rybak D. - IPPT PAN
Rinoldi C. - IPPT PAN
Nakielski P. - IPPT PAN
Pierini F. - IPPT PAN

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